Moleculin Announces Breakthrough Discovery for its WP1066

On December 4, 2018 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company focused on the development of oncology drug candidates, all of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that its own sponsored research has now confirmed a recent published study demonstrating the ability of its clinical-stage immuno-stimulating STAT3 inhibitor, WP1066, to inhibit a key immune checkpoint target known as PD-L1 (Press release, Moleculin, DEC 4, 2018, View Source [SID1234531871]).

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"We have known for some time that WP1066 had the potential to stimulate a natural immune response," commented Dr. Donald Picker, Moleculin’s Chief Science Officer. "But, this data suggests that our drug may be capable of having a major impact on the field of checkpoint blockades. With this information combined with findings from other recently published studies demonstrating the impotant role of STAT3 in cancer immunology, we plan to run additional in vitro and in vivo studies, some of which are already underway, with WP1066 in combination with well-known checkpoint inhibitors to gather more data on this response."

Walter Klemp, Moleculin’s Chairman and CEO added, "This potential was initially reported in a 2017 Japanese study (Journal of clinical and experimental hematopathology, Vol. 57 No.1, 21-25, 2017), but we have now been able to confirm this activity with our own sponsored research at MD Anderson. Also, very recent independent research (Front Pharmacol. 2018 May 22;9:536. doi: 10.3389/fphar.2018.00536. eCollection 2018.) has linked STAT3, HIF1-a and c-Myc (all targets of WP1066) to the mechanism (a ligand known as PD-L1) believed to be largely responsible for resistance to current checkpoint blockade therapies. We believe this could put WP1066 center-stage in the field of immunotherapy. It’s potentially a tremendous breakthrough for our company."

Celltrion Healthcare presents positive results for CT-P10, biosimilar rituximab, in advanced follicular lymphoma at the American Society of Hematology Meeting 2018

On December 4, 2018 Celltrion Healthcare reported new data at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting (ASH) (Free ASH Whitepaper) 2018, which shows that the efficacy and safety of CT-P10 is comparable to reference rituximab in patients with advanced follicular lymphoma (AFL) over two years (Press release, Celltrion, DEC 4, 2018, View Source [SID1234531887]).1

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The efficacy and safety of CT-P10 was evaluated in a randomized, double-blind, Phase III study which evaluated the overall survival (OS), progression-free survival (PFS), and sustained response in comparison to the reference biologic rituxan. The median follow-up duration was 23 months.i

140 patients were enrolled in a 1:1 ratio and 124 patients completed eight cycles of chemotherapy (R-CVP induction). 122 patients (62 patients in the CT-P10 group and 60 patients in the reference rituximab group) who showed response during the induction period, entered the maintenance period where a total of 12 cycles of rituximab monotherapy was to be administered every two months.i

The results showed that at the median follow-up duration of 23 months, the updated efficacy data in AFL patients demonstrated comparable OS (2-year OS of 93.2% and 95.3% for CT-P10 and reference rituximab, respectively) and PFS (2-year PFS was 75.2% and 73.5% for CT-P10 and reference rituximab, respectively). In terms of sustained response, the proportion of patients who showed relapse or disease progression after achieving overall response was 19.4% (13/67) in the CT-P10 group and 21.3% (13/61) in the reference rituximab group. CT-P10 was also well-tolerated and its safety profile including immunogenicity of CT-P10 was comparable to that of reference rituximab over 23 months of treatment.i

Christian Buske, Professor, Medical Director at the Comprehensive Cancer Center Ulm, Germany, Institute of Experimental Cancer Research and Attending Physician and Professor of Medicine at the Medical Department for Internal Medicine III, Hematology/Oncology, University Hospital Ulm said, "CT-P10 has already demonstrated non-inferiority of efficacy compared with reference rituximab combined with CVP in previously untreated AFL. The study results presented today have further strengthened these findings, showing no statistically meaningful difference between CT-P10 and reference rituximab for over two years and demonstrating a proven safety profile. I believe that these results will help to further increase physician confidence in using rituximab biosimilars and will broaden AFL patient access to efficacious and affordable therapies."

Mr HoUng Kim, Head of Strategy and Operations Division, Celltrion Healthcare, said: "The two-year study marks another significant milestone for Celltrion Healthcare, showing that CT-P10 is comparable to reference rituximab in terms of overall survival and progression-free survival. Now that CT-P10 is approved in the US, the availability of the first rituximab biosimilar has the potential to significantly improve access to rituximab for patients with non-Hodgkin’s lymphoma indications. As a cost-effective alternative to the reference product, CT-P10 will reduce the burden on healthcare systems resulting in better patient outcomes."

Also presented at ASH (Free ASH Whitepaper) and published in The Lancet Haematology, is data from the CT-P10 3.4 LTBFL trial which aimed to demonstrate therapeutic equivalence of CT-P10 to reference rituximab (as monotherapy) in patients with previously untreated Low Tumor Burden Follicular Lymphoma (LTBFL).2

The results showed that CT-P10 was well-tolerated and the safety profile was comparable to that of reference rituximab over seven months. 108 (83%) of 130 patients assigned to CT-P10 and 104 (81%) of 128 assigned to rituximab achieved an overall response by month seven (treatment difference estimate 1·8%; 90% CI –6·43 to 10·20) and therapeutic equivalence was shown (90% CIs were within the prespecified margin of 17%).ii

CT-P10 is the first rituximab biosimilar to be approved in the United States.3

— Ends—

Notes to editors:

About CT-P10 (biosimilar rituximab)
CT-P10 is a mAb that targets CD20, a transmembrane protein found on the surface of most B cells. By binding specifically to CD20, CT-P10 depletes B cells by three main mechanisms: Induction of apoptosis, stimulation of CDC (complement-dependent cytotoxicity) and stimulation of ADCC (antibody-dependent cell-mediated cytotoxicity). CT-P10 is approved in the EU for the treatment of patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. Further details of the approved indications and safety information for CT-P10 are available in the summary of product characteristics (SmPC).4 Celltrion and Teva Pharmaceutical Industries Ltd. entered into an exclusive partnership in October 2016 to commercialize CT-P10 (Truxima) in the U.S. and Canada.

About Advanced FL
Follicular lymphomas are the second most frequent subtype of nodal lymphoid malignancies in Western Europe5 and are a subtype of NHL.6 It is a slow-growing lymphoma that develops from B lymphocytes (B cells). It is characterised by painless swelling of the lymph nodes, fever for no apparent reason, drenching night sweats, fatigue, infections and bleeding. Most cases are advanced at the time of diagnosis but since the advent of rituximab, overall survival has increased to in excess of 20 years. It is called ‘follicular’ lymphoma because the abnormal lymphocytes often collect in lymph nodes in clumps that are known as ‘follicles’. Follicular lymphoma is more common in people aged over 65, but it can occur in people of any age.

AVEO Oncology Announces Extension of Debt Facility Interest Only Period

On December 4, 2018 AVEO Oncology (NASDAQ:AVEO) reported a six-month extension to the interest only period under its existing amended and restated loan and security agreement with Hercules Capital, Inc. (Hercules) (Press release, AVEO, DEC 4, 2018, View Source [SID1234531888]). The extension was granted as a result of achieving certain predefined requirements under the agreement, including successfully meeting the primary endpoint of the Company’s Phase 3 TIVO-3 study of tivozanib in refractory advanced or metastatic renal cell carcinoma (RCC), by demonstrating a significant improvement in progression free survival.

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The Company will begin making principal payments on the $20.0 million facility starting on August 1, 2019. AVEO believes that its available cash, cash equivalents, and marketable securities, together with the extension of the interest only period under the Hercules loan agreement, which results in deferment of principal payments, will allow it to fund planned operations into Q3 2019. This estimate assumes no receipt of additional milestones from AVEO’s partners, no additional funding from new partnership agreements, no additional equity or debt financings, and no sales of equity through the exercise of outstanding warrants issued in connection with the 2016 private placement or outstanding warrants issued in connection with the settlement of the securities class action litigation.

"Extension of our cash runway takes us through several key anticipated milestones, with the presentation of our TIVO-3 data, including a planned update to the preliminary OS analysis which will contain additional patient data recovered in the ongoing OS sweep, and potential submission of a New Drug Application with the FDA for tivozanib in RCC. Both milestones are expected in the first half of 2019," said Michael Bailey, president and chief executive officer. "We also look forward to making important progress within this period on our immunotherapy combination strategy, the third pillar of our tivozanib strategy."

KOL webcast and conference call (on Tuesday, December 4, at 5pm CET): Innate Pharma announces updated results that support advancement of IPH4102 in refractory Sézary syndrome at the American Society of Hematology (ASH) 2018 annual meeting

On December 4, 2018 Innate Pharma reported its updated results that support advancement of IPH4102 in refractory Sézary syndrome at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 annual meeting (Press release, Innate Pharma, DEC 4, 2018, View Source [SID1234531856]).

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Pierre Dodion, Chief Medical Officer, Innate Pharma, will be joined by Prof. Martine Bagot, Head of Dermatology Department at the Saint Louis Hospital, Paris and lead investigator of the study, for a live webcast and conference call with a Q&A session on Tuesday, December 4 at 5pm CET to discuss the announcement.

The presentation and access to the live webcast will be available at this link: View Source

Participants can also join the conference call using the following dial-in numbers:

Location

Purpose

Phone number

France

Participant

+33 (0)1 76 77 22 57

United Kingdom

Participant

+44 (0)330 336 9411

United States

Participant

+1 929-477-0324

Standard International Access

Participant

0800 279 7204

The participation code is: 4535688

Actinium Pharmaceuticals Highlights Analysis of Pivotal Iomab-B Phase 3 SIERRA Trial Presented in Oral Session at ASH Annual Meeting

On December 4, 2018 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) reported that additional data from an updated analysis of the pivotal Iomab-B Phase 3 SIERRA trial were highlighted last night in an oral presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, DEC 4, 2018, View Source [SID1234531873]). The SIERRA trial is the only ongoing Phase 3 trial offering a bone marrow transplant (BMT) to patients 55 years of age or older with active, relapsed or refractory acute myeloid leukemia (AML). Data in the table below were presented in the oral session and are updated from those at the time of abstract submission. Preliminary data strongly support the feasibility and safety of re-induction and targeted conditioning with Iomab-B prior to a BMT.

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Preliminary Feasibility and Safety Data

Randomized to
Iomab-B Study Arm
(N=19)

Randomized to
Conventional Care
(N=19)

Randomized to
Conventional Care,
No Remission, and
Crossed Over (N=10)

Number of Patients
Receiving BMT after
receiving therapy

100% (18/18)

(1 patient did not
receive therapeutic
Iomab-B dose)

21% (4/19)

100% (10/10)

Blast % at
Randomization

Median: 30%

Range: 4* -74

Median: 26%

Range: 6-97

At Randomization
24% (6-70)
At Crossover 45%
(10-70)

Days to BMT

(post-randomization)

Median: 28

Range: 23-38

Median: 67

Range: 66-86

Median: 66

Range: 57-161

Days to Absolute
Neutrophil
Engraftment

Median:13

Range: 9 – 22

Not entered

Median:13

Range: 9 – 20

Days to Platelet
Engraftment

Median: 16

Range: 13 – 26

Not entered

Median:17

Range: 10 – 20

100-Day Non-
Relapse Mortality

0% (0/18)

25% (1/4 – septic
shock)

10% (1/10 – diffuse
alveolar hemorrhage)

*1 patient with 4% blasts in the marrow had circulating AML blasts

Other Key Highlights:

15 of 19 (79%) patients in the control arm failed to achieve a complete response
67% (10/15) of patients eligible for crossover successfully transplanted with Iomab-B
All patients receiving Iomab-B engrafted despite active disease with high blast count (median 30%, or median 45% for crossover patients)
Patients receiving Iomab-B received a BMT more quickly post-randomization (28 days) than patients receiving conventional care (67 days)
In the conventional care arm, there was no difference in time to BMT for patients that crossed over to Iomab-B (66 days) compared to those achieving complete remission with conventional care (67 days)
No Grade 3 or 4 Iomab-B infusion related reactions with all Iomab-B infusions completed
No non-relapse mortality in patients randomized to Iomab-B arm
Abstract #1017: Targeted Conditioning of Iomab-B (131I-anti-CD45) Prior to Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care in Relapsed or Refractory Acute Myeloid Leukemia (AML): Preliminary Feasibility and Safety Results from the Prospective, Randomized Phase 3 Sierra Trial

Dr. Edward Agura, Medical Director of Bone Marrow Transplantation at Baylor University Medical Center said, "Given that more than two thirds of patients who are diagnosed with AML are 55 years of age or older, there exists a significant unmet medical need to broaden transplant access and improve outcomes for these patients. The data from the SIERRA trial thus far are highly encouraging as they demonstrate that Iomab-B can enable a potentially curative transplant in patients with active disease, including those patients with progressing disease who did not achieve a response on conventional care. The nearly universal and rapid engraftment of patients receiving Iomab-B, together with no 100-day non-relapse mortality, is particularly compelling as these results have not been achieved with conventional care."

The 150 patient SIERRA study is a multi-center randomized trial that will compare outcomes of patients who receive Iomab-B and a BMT to those patients receiving physician’s choice of salvage chemotherapy, defined as conventional care, as no standard of care exists for this patient population. AML patients with active, relapsed or refractory AML have dismal prognoses and are typically not offered curative transplant as an option. This is largely because salvage treatments have a limited ability to produce a complete remission, which is necessary prior to BMT if conventional BMT is to be successful. However, with Iomab-B targeted conditioning, a complete remission prior to starting the Iomab-B conditioning is not necessary for a successful transplant.

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "We believe that Iomab-B represents a potentially disruptive modality for targeted conditioning. The preliminary data from the SIERRA trial presented at ASH (Free ASH Whitepaper) exceeded our expectations regarding feasibility and safety, which adds to the already extensive body of research and data demonstrating the utility of Iomab-B for targeted conditioning in multiple hematologic indications. With this data in hand we are highly motivated to complete the SIERRA trial, which will serve as the beachhead for our multi-target, multi-disease pipeline for targeted conditioning, where we are committed to expanding our leadership position."